Research Article: Blood pressure and expression of microRNAs in whole blood

Date Published: March 9, 2017

Publisher: Public Library of Science

Author(s): Zhou Zhang, Brian Thomas Joyce, Jacob K. Kresovich, Yinan Zheng, Jia Zhong, Ruchi Patel, Wei Zhang, Lei Liu, Chang Dou, John P. McCracken, Anaité Díaz, Valeria Motta, Marco Sanchez-Guerra, Shurui Bian, Pier Alberto Bertazzi, Joel Schwartz, Andrea A. Baccarelli, Sheng Wang, Lifang Hou, Zhanjun Jia.

http://doi.org/10.1371/journal.pone.0173550

Abstract

Blood pressure (BP) is a complex, multifactorial clinical outcome driven by genetic susceptibility, behavioral choices, and environmental factors. Many molecular mechanisms have been proposed for the pathophysiology of high BP even as its prevalence continues to grow worldwide, increasing morbidity and marking it as a major public health concern. To address this, we evaluated miRNA profiling in blood leukocytes as potential biomarkers of BP and BP-related risk factors.

The Beijing Truck Driver Air Pollution Study included 60 truck drivers and 60 office workers examined in 2008. On two days separated by 1–2 weeks, we examined three BP measures: systolic, diastolic, and mean arterial pressure measured at both pre- and post-work exams for blood NanoString nCounter miRNA profiles. We used covariate-adjusted linear mixed-effect models to examine associations between BP and increased miRNA expression in both pooled and risk factor-stratified analyses.

Overall 43 miRNAs were associated with pre-work BP (FDR<0.05). In stratified analyses different but overlapping groups of miRNAs were associated with pre-work BP in truck drivers, high-BMI participants, and usual alcohol drinkers (FDR<0.05). Only four miRNAs were associated with post-work BP (FDR<0.05), in ever smokers. Our results suggest that many miRNAs were significantly associated with BP in subgroups exposed to known hypertension risk factors. These findings shed light on the underlying molecular mechanisms of BP, and may assist with the development of a miRNA panel for early detection of hypertension.

Partial Text

Hypertension (HTN), defined as systolic blood pressure (SBP) above 140 mmHg or diastolic blood pressure (DBP) above 90 mmHg, is a major public health concern worldwide [1, 2]. Despite our understanding of the disease and availability of treatments, 80 million adults in the US [3] as well as 266 million adults in China [4] suffer from HTN, indicating a substantial unrelieved public health burden. With primary prevention efforts (e.g., the DASH diet) [5, 6] largely unsuccessful in populations in recent decades, secondary prevention through earlier disease detection may aid reducing HTN-related health disparities and economic burdens. In particular analyses of whole blood have found shifts in environment-induced gene expression that presage systemic pro-inflammatory processes [7–9] and can predict future cardiovascular disease risk [10]. Greater insight into molecular mechanisms related to elevated blood pressure (EBP), a physiological event related to clinical HTN, can assist in addressing its current unmet public health burden.

To our knowledge this study is the first to evaluate miRNA profiling from blood leukocytes in relation to BP among a cohort of Chinese workers. We observed that both pre- and post-work SBP, DBP, and MAP were all higher in participants that were male, had higher BMI, or were smokers; all traditional risk factors of HTN [33]. Our pooled analysis also revealed 43 miRNAs associated with one or more BP measures but only at the pre-work exams. The stratified analyses showed varied significant associations between miRNAs and pre-work BP measures by strata of subject characteristics including occupation, BMI, and usual alcohol drinking, as well as only ever-smokers had a panel of miRNAs significantly associated with post-work BP.

 

Source:

http://doi.org/10.1371/journal.pone.0173550